Mitochondrial-targeted Antioxidant Enhancing Effects on Vascular Endothelial Function in Middle-aged and Older Adults Is Influenced by Cardiorespiratory Fitness

Vascular endothelial dysfunction in middle-aged and older (MA/O, ≥ 45 y) adults is partly attributable to excess mitochondrial reactive oxygen species (mtROS) production. Aerobic exercise preserves endothelial function in preclinical models via lower mtROS and mitigates the deleterious effects of aging on cardiorespiratory fitness (CRF). However, the acute effects of a mitochondrial-targeted antioxidant on age-related vascular endothelial function in the context of CRF are currently unknown. We hypothesized lower CRF resulting from a physically inactive lifestyle contributing to age-related endothelial dysfunction is mediated via greater mtROS in humans. In a double-blind, randomized, placebo-controlled crossover study design MA/O adults were divided into two groups: exercisers (EX, n=11, age 60.0 ± 4.0 y, BMI 25.0 ± 0.9 kg/m 2 ) and non-exercisers (NEX, n=12, age 64.0 ± 2.8 y, BMI 28.2 ± 1.0 kg/m 2 ). CRF, assessed via VO 2max , was measured on a cycle ergometer from an incremental ramp protocol (10 or 20 watts/min). Vascular endothelial function from brachial artery flow mediated dilation (FMD BA ) was acquired before (pre-ingestion) and ~1 h after MitoQ (single dose, 80 mg) or placebo supplementation. A two-way repeated measures ANOVA with a Bonferroni post-hoc analysis was used to determine the effects of MitoQ and placebo on FMD BA . Compared to placebo, MitoQ increased FMD BA in NEX (pre: 4.9 ± 0.4 vs post: 7.0 ± 0.4 %, p0.05) or brachial artery diameter (pre: 0.25 ± 0.02 vs post: 0.26 ± 0.02 mm, p>0.05) in EX. CRF was positively correlated with baseline FMD BA (n=17, r=0.56, p=0.01) whereas the change in FMD BA with MitoQ was inversely correlated with CRF (r=-0.54, p=0.02). These data demonstrate the acute MitoQ-enhancing effects on vascular endothelial function in MA/O adults is attributable, in part, to greater mtROS in physically inactive adults with lower CRF. Funding for this study was provided, in part, by Ball State University ASPiRE internal research grant (N.A. Carlini). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.